The ability to flexibly learn and remember is one of the hallmarks of human cognition and is essential for healthy functioning, as becomes apparent in severe cases of dementia. The proposed work seeks to understand how the brain activity occurring during learning influences the brain activity occurring during remembering. This work focuses on three neural processes: 1) Activity in the hippocampus during learning, which is associated with subsequently remembering the learned material, 2) Activity in the ventrolateral prefrontal cortex (VLPFC) during remembering, which is associated with how difficult that information is to remember, and 3) Reactivation during remembering of the regions that were active during learning, which is associated with vividly re-experiencing the remembered event. Our theory proposes that specific relationships exist among these activity patterns. Specifically, we predict that those memories associated with high hippocampal activity during learning will be associated with 1) low VLPFC activity during retrieval, because those memories will be learned better and easier to remember, 2) more and faster reactivation during retrieval, because those memories will be learned better and re-experienced more vividly and quickly, and 3) faster reactivation during retrieval, because those memories will be learned better and re-experienced more quickly. In the proposed studies, these predictions will be tested by recording brain activity while participants 1) learn associations between nouns and sounds or pictures and 2) subsequently try to remember the sounds or pictures when given the nouns as cues. In study 1, brain activity will be recorded during learning and remembering using functional magnetic resonance imaging (fMRI), a technique ideally suited to determining precisely where brain activity is occurring. Predictions 1 and 2 will be tested by comparing the magnitude of hippocampal activity during learning with 1) the magnitude of VLPFC activity during remembering and 2) the magnitude of reactivation of picture and sound regions during remembering, respectively. In study 2, brain activity will be recorded during learning with fMRI and during remembering with magnetoencephalography (MEG), a technique ideally suited to determining precisely when brain activity is occurring. Prediction 3 will be tested by comparing the magnitude of hippocampal activity during learning with the speed of reactivation during remembering. This research will provide a better understanding of how the different neural processes that occur during learning and remembering influence one another. PUBLIC HEALTH RELEVANCE: When ability to flexibly learn and remember becomes compromised, cognitive function and quality of life can decline markedly. Therefore, an understanding of how these processes occur in the brain is essential to understanding a number of neurological and psychological disorders, including but not limited to stroke, dementia, amnesia, schizophrenia, depression, and post-traumatic stress disorder (PTSD). In fact, damage to the medial temporal lobe specifically has been linked to memory problems in Alzheimer's disease, aging, and schizophrenia.